Am J Perinatol 2005; 22(8): 449-455
DOI: 10.1055/s-2005-918888
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Effect of Early Recombinant Erythropoietin and Enteral Iron Supplementation on Blood Transfusion in Preterm Infants

Gülcan Türker1 , Nazan Sarper2 , Ayşe Sevim Gökalp1 , Hale Usluer1
  • 1Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
  • 2Division of Haematology, Department of Pediatrics, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
Further Information

Publication History

Publication Date:
19 October 2005 (online)

ABSTRACT

Premature infants < 1500 g were randomly assigned to study and control groups. In the study group, 42 premature infants received recombinant human erythropoietin (r-Hu EPO) 750 U/kg per week subcutaneously from day 5 to 40 and enteral iron supplementation of 2 to 6 mg/kg/d beginning on day 14 provided that they were receiving at least 50% energy intake orally. In the control group, 51 infants received the same dose of enteral iron supplementation beginning at the end of the fourth week. At the end of a 12-week monitoring period, r-Hu EPO combined with early enteral iron reduced transfusion needs only in the subgroup < 1000 g. r-Hu EPO and early iron treatment had no effect on the development of severe retinopathy of prematurity, intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. We suggest that r-Hu EPO combined with early enteral iron is both effective and safe in infants < 1000 g.

REFERENCES

  • 1 Shannon K M, Naylor G S, Torkildson J C et al.. Circulating erythroid progenitors in the anemia of prematurity.  N Engl J Med. 1987;  317 728-733
  • 2 Rhondeau S M, Christensen R D, Ross M P, Rothstein G, Simmons M A. Responsiveness to recombinant human erythropoietin of marrow erythroid progenitors from infants with anemia of prematurity.  J Pediatr. 1988;  112 935-940
  • 3 Strauss R G. Recombinant erythropoietin for the anemia of prematurity: still a promise, not a panacea.  J Pediatr. 1997;  131 653-655
  • 4 Widness J A, Seward V J, Kromer I J, Burmeister L F, Bell E F, Strauss R G. Changing patterns of red blood cell transfusions in very low birth weight infants.  J Pediatr. 1996;  129 680-687
  • 5 Soubasi V, Kremenopoulos G, Diamandi E, Tsantali C, Tsakiris D. In which neonates does early recombinant human erythropoietin treatment prevent anemia of prematurity? Results of a randomized, controlled study.  Pediatr Res. 1993;  34 675-679
  • 6 Bechensteen A G, Hågå P, Halvorsen S et al.. Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity.  Arch Dis Child. 1993;  69 19-23
  • 7 Juul S E, Joyce A E, Zhao Y, Ledbetter D J. Why is erythropoietin present in human milk? Studies of erythropoietin receptors on enterocytes of human and rat neonates.  Pediatr Res. 1999;  46 263-268
  • 8 Ledbetter D J, Juul S E. Erythropoietin and the incidence of necrotizing enterocolitis in infants with very low birth weight.  J Pediatr Surg. 2000;  35 178-182
  • 9 Hesse L, Eberl W, Schlaud M, Poets C F. Blood transfusion: iron load and retinopathy of prematurity.  Eur J Pediatr. 1997;  156 465-470
  • 10 Silvers K M, Gibson A T, Russell J M, Powers H J. Antioxidant activity, packed cell transfusions, and outcome in premature infants.  Arch Dis Child Fetal Neonatal Ed. 1998;  78 F214-F219
  • 11 Franz A, Mihatsch W, Sander S, Kron M, Pohlandt F. Prospective randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams.  Pediatrics. 2000;  106 700-706
  • 12 Gallagher P G, Ehrenkranz R A. Nutritional anemias in infancy.  Clin Perinatol. 1995;  22 671-692
  • 13 Strauss R G. Red blood cell transfusion practices in the neonate.  Clin Perinatol. 1995;  22 641-655
  • 14 Himelstein B P, Douglas S D, Cohen A R. Hematology and immunology. In: Polin RA, Ditmar MF Pediatrics Secrets Philadelphia; Hanley & Belfus 1997: 219-253
  • 15 Committee for the Classification of the Retinopathy of Prematurity . An international classification of infection or inflammation of retinopathy of prematurity.  Arch Ophthalmol. 1984;  102 1130-1134
  • 16 Northway Jr W H, Rosan R C, Porter D Y. Pulmonary disease following respirator therapy for hyaline membrane disease.  N Engl J Med. 1967;  276 357-368
  • 17 Bell R S, Graham C B, Stevenson J K. Roentgenologic and clinical manifestations of neonatal necrotizing enterocolitis: experience with 43 cases.  Am J Roentgenol Radium Ther Nucl Med. 1971;  112 123-134
  • 18 Papile L A, Burstein J, Burstein R. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birthweight less than 1500 grams.  J Pediatr. 1978;  92 529-534
  • 19 Rigourd V, Kieffer F, Dommergues M A et al.. Erythropoietin administration to preterm infants: comparison between subcutaneous and intravenous route [in French].  Arch Pediatr. 2004;  11 319-326
  • 20 Ohls R K, Veerman M W, Christensen R D. Pharmacokinetics and effectiveness of recombinant erythropoietin administered to preterm infants by continuous infusion in parenteral nutrition solution.  J Pediatr. 1996;  128 518-523
  • 21 Juul S E. Enterally dosed recombinant human erythropoietin does not stimulate erythropoiesis in neonates.  J Pediatr. 2003;  143 321-326
  • 22 Maier R F, Obladen M, Kattner E et al.. High-versus low-dose erythropoietin in extremely low birth weight infants.  J Pediatr. 1998;  132 866-870
  • 23 Kivivuori S M, Virtanen M, Raivio K O, Viinikka L, Siimes M A. Oral iron is sufficient for erythropoietin treatment of very low birth weight infants.  Eur J Pediatr. 1999;  158 147-151
  • 24 Gutteridge J M. Fate of oxygen free radicals in extracellular fluids.  Biochem Soc Trans. 1982;  10 72-73
  • 25 McDonald M C, Abrams S A, Schanler R J. Iron absorption and red blood cell incorporation in premature infants fed an iron-fortified infant formula.  Pediatr Res. 1998;  44 507-511
  • 26 Brown M S, Shapiro H. Effect of protein intake on erythropoiesis during erythropoietin treatment of anemia of prematurity.  J Pediatr. 1996;  128 512-517
  • 27 Franz A R, Pohlandt F. Red blood cell transfusion in very and extremely low birth weight infants under restrictive transfusion guideliness: is exogenous erythropoietin necessary?.  Arch Dis Child Fetal Neonatal Ed. 2001;  84 F96-F100
  • 28 Maier R F, Obladen M, Scigalla P et al.. The effect of epoetin beta (recombinant human erythropoietin) on the need from transfusion in very low birth weight infants.  N Engl J Med. 1994;  330 1173-1178
  • 29 Donato H, Vain N, Rendo P et al.. Effect of early versus late administration of human recombinant erythropoietin on transfusion requirements in premature infants: results of a randomized, placebo-controlled, multicenter trial.  Pediatrics. 2000;  105 1066-1072
  • 30 Ohls R K, Ehrenkranz R A, Wright L L et al.. Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial.  Pediatrics. 2001;  108 934-942
  • 31 Ohls R, Osborne K A, Christensen R D. Efficacy and cost analysis of treating very low birth weight infants with erythropoietin during their first two weeks of life: a randomized placebo-controlled trial.  J Pediatr. 1995;  126 421-426
  • 32 Williamson P, Griffiths G, Norfolk D, Levene M. Blood transfusions and human recombinant erythropoietin in premature newborn infants.  Arch Dis Child Fetal Neonatal Ed. 1996;  75 F65-F68
  • 33 Ohls R K, Harcum J, Schibler K R, Christensen R D. The effect of erythropoietin on the transfusion requirements of preterm infants weighing 750 g or less: a randomized, double-blind, placebo-controlled study.  J Pediatr. 1997;  131 661-665
  • 34 Meyer M P, Meyer J H, Commerford A et al.. Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo controlled study.  Pediatrics. 1994;  93 918-923
  • 35 Meyer M P, Sharma E, Carsons M. Recombinant erythropoietin and blood transfusion in selected preterm infants.  Arch Dis Child Fetal Neonatal Ed. 2003;  88 F41-F45
  • 36 Yeo C L, Choo S, Ho L Y. Effect of recombinant human erythropoietin on transfusion needs in preterm infants.  J Paediatr Child Health. 2001;  37 352-358
  • 37 Drack A V. Preventing blindness in premature infants.  N Engl J Med. 1998;  338 1620-1621
  • 38 James L, Greenough A, Naik S. The effect of blood transfusion on oxygenation in premature ventilated neonates.  Eur J Pediatr. 1997;  156 139-141
  • 39 Cooke R W, Clark D, Hickey-Dwyer M, Weindling A M. The apparent role of blood transfusion in the development of retinopathy of prematurity.  Eur J Pediatr. 1993;  152 833-836
  • 40 Shaw J CL. Iron absorption by the premature infants: the effect of transfusion and iron supplementation on the serum ferritin levels.  Acta Paediatr Scand. 1982;  299 S83-S89
  • 41 Lackmann G M, Schnieder C, Bohner J. Gestational age-dependent reference values for iron and selected proteins of iron metabolism in serum premature human neonates.  Biol Neonate. 1998;  74 208-213
  • 42 Siimes M A, Addiego J E, Dallman P R. Ferritin in serum, diagnosis of iron deficiency and overload in infants and children.  Blood. 1974;  43 581-590
  • 43 Seiberth V, Linderkamp O. Risk factors in retinopathy of prematurity: a multivariate statistical analysis.  Ophthalmologica. 2000;  214 131-135
  • 44 Pollak A, Hayde M, Hayn M et al.. Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants.  Pediatrics. 2001;  107 78-85

Gülcan TürkerM.D. 

Kocaeli Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve

Hastalıkları Anabilim Dalı, Sopalı, Derince 41900, Kocaeli, Turkey